Change of Coagulation Factor Ⅷ and Antithrombin Ⅲ Activity in Bank-Stored Blood

Coagulation factor Ⅷ and antithrombin Ⅲ activity were detected in 15 health donors. It was found that antithrombin Ⅲ activity decreased obviously 12 h after blood drawing. It lost 56 % of the activity at the 3rd day, and 70 % of the activity at the 7th day. FⅧ:c showed no obvious change after 24 h, until the 3rd day. It lost 40 %-60 % of the activity after 36 h and was reduced to the 30 % of the original activity at the 5th day. Our results suggested that at the 3rd day coagulation factor Ⅷ of bank stored blood can be used to replenish antithrombin Ⅲ, while bank stored blood in one day can be used to replenish FⅧ.

Risk Factors for Mortality in Critically Ill Patients with Coagulation Abnormalities:A Retrospective Cohort Study

Objective Coagulation abnormalities are common and prognostically significant in intensive care units(ICUs)and are associated with increased mortality.This study aimed to explore the association between the levels of coagulation markers and the risk of mortality among ICU patients with coagulation abnormalities.Methods This retrospective study investigated patients with coagulation abnormalities in the ICU between January 2021 and December 2022.The initial point for detecting hemostatic biomarkers due to clinical assessment of coagulation abnormalities was designated day 0.Patients were followed up for 28 days,and multivariate logistic regression analysis was utilized to identify risk factors for mortality.Results Of the 451 patients analyzed,115 died,and 336 were alive at the end of the 28-day period.Multivariate analysis revealed that elevated thrombin-antithrombin complex(TAT),tissue plasminogen activator inhibitor complex(tPAIC),prolonged prothrombin time,and thrombocytopenia were independent risk factors for mortality.For nonovert disseminated intravascular coagulation(DIC)patients,older age and thrombocytopenia were associated with increased risks of mortality,whereas elevated levels of plasminα2-plasmin inhibitor complex(PIC)were found to be independent predictors of survival.In patients with overt DIC,elevated levels of tPAIC were independently associated with increased risks of mortality.Nevertheless,thrombocytopenia was independently associated with increased risks of mortality in patients with pre-DIC.Conclusion Coagulation markers such as the TAT,tPAIC,PIC,and platelet count were significantly associated with mortality,underscoring the importance of maintaining a balance between coagulation and fibrinolysis.These findings highlight the potential for targeted therapeutic interventions based on specific coagulation markers to improve patient outcomes.

ABO Blood Groups and Their Relationship with Coagulation Factor VIII in Healthy Adults

Background: ABO blood group distribution defers with racial and geographic variations. They are related to diseases like cardiovascular diseases, cerebral thromboembolism. ABO blood group system may influence coagulation factor VIII which may increase the future risk of thrombosis. Aim: To assess the relation of ABO blood group with coagulation factor VIII in healthy adults. Material and Methods: A prospective type of analytical cross-sectional study was conducted in the Department of Physiology, Dhaka Medical College, Dhaka from July 2019 to June 2020. After obtaining ethical clearance, a total of 190 healthy adults were selected from different areas of Dhaka city based on inclusion and exclusion criteria, with ages ranging from 18 - 45 years. The subjects were interviewed and detailed history regarding personal, family, medical and drug were taken. Prior to sample collection, informed written consent was taken from the participants. Individuals of blood group A were selected as group A, blood group B as group B, blood group AB as group AB and blood group O as group O. Coagulation factor VIII was measured in the Department of Hematology and BMT Unit, Dhaka Medical College Hospital, Dhaka. Blood grouping was done in the Department of Physiology, Dhaka Medical College, Dhaka. Statistical Analysis: For statistical analysis, ONE way ANOVA followed by Bonferroni test were considered using SPSS 25.0 version. Results: In this study, blood group B was most common (33.2%). Coagulation factor VIII was significantly higher (p < 0.001) in blood group A (105.76% ± 11.82%), B (112.00% ± 15.02%), AB (109.80% ± 11.93%) than blood group O (82.00% ± 12.86%). No significant difference was observed among A, B and AB blood groups regarding coagulation factor VIII. Conclusions: It can be concluded that blood group A, B, AB individuals may have more chance of thrombosis due to significantly higher coagulation factor VIII than blood group O individuals.

Effects of blood purification combined with Xuebijing on coagulation, immunity, inflammation and vascular factors in sepsis patients

Objective:To investigate the effects of blood purification combined with Xuebijing on coagulation, immunity, inflammation and vascular factors in sepsis patients.Methods: 82 sepsis patients admitted to the Xuzhou Municipal Hospital Affiliated to Xuzhou Medical University from January 2017 to January 2019 were selected as the research objects. According to the random drawing method, 41 cases in the control group and 41 cases in the observation group were divided into two groups. The control group was treated with routine western medicine, including antibiotic therapy, blood sugar control, respiratory support and nutritional support. The observation group was treated with continuous blood purification combined with Xuebijing on the basis of the control group. The changes of coagulation index, immune factor, inflammatory reaction and vascular factor levels were observed before and after treatment in two groups.Results:After treatment, the levels of activated partial thromboplastin time (APTT), prothrombin time (PT), D-Dimer (DD), CD8+, procalcitonin (PCT), Tumor Necrosis Factor-α (TNF-α), high mobility group box-B1 (HMGB1) and soluble fms-like tyrosine kinase,(sFLT)in the two groups were significantly lower than those before treatment, while the levels of CD4+, CD4+/CD8+, and vascular endothelial growth factor (VEGF) were significantly higher than those before treatment;and the levels of APTT, PT, DD, CD8+, PCT, TNF-a, HMGB1 and sFLT in the observation group after treatment were significantly lower than those in the control group, the levels of CD4+, CD4+/CD8+, and VEGF in the observation group after treatment were significantly higher than those in the control group, there was a significant difference in each indexes between the different groups after treatment. Conclusions:Continuous blood purification combined with Xuebijing therapy can effectively improve the coagulation function of sepsis patients, enhance the immune mechanism of patients, reduce inflammation and protect vascular endothelial function. It has clinical popularization significance.

Effect of Dan seven soft capsule adjuvant therapy on serum inflammatory factors, coagulation function and blood rheology indexes in patients with acute hemorrhagic cerebrovascular disease

Objective: To investigate the effect of Dan seven soft capsule on the treatment of acute hemorrhagic cerebrovascular disease and the influence of serum inflammatory factors, coagulation function and blood rheology indexes. Methods: A total of 112 cases of patients with acute hemorrhagic cerebrovascular disease, according to the random data table were divided into the control group (n=57) and observation group (n=55), the patients in the control group received routine treatment combined with edaravone, on the basis of the treatment of the control group, the observation group was treated with Dan seven soft capsule. The serum levels of inflammatory factors, coagulation function and blood rheology indexes were compared between the two groups before and after treatment. Results: Before treatment, there were no significant difference in the inflammatory factors (hs-CRP, TNF-α and IL-6), blood coagulation function (FIB, PT and APTT) and hemorheology (high cut whole blood viscosity, low cut whole blood viscosity and plasma viscosity) levels between the control group and observation group. Compared with the levels of the same group before treatment, two groups of hs-CRP, TNF-α, IL-6, FIB, high cut whole blood viscosity, low cut whole blood viscosity and plasma viscosity level after treatment were significantly decreased, and levels in the observation group were significantly lower than those in the control group;Compared with the group before treatment, the levels of PT and APTT in the two groups were significantly increased, and the observation group was significantly higher than the control group. Conclusion: Dan seven soft capsule in the treatment of acute hemorrhagic cerebrovascular disease can effectively reduce the level of serum inflammatory factors, improve coagulation function and blood rheology index, it has an important clinical value.

Preparation and Structure of a New Coagulation Factor XI Catalytic Domain for Drug Discovery

Human blood coagulation factor XI （FXI） is a key enzyme in the amplification phase of blood coagulation cascade, and is recognized as an important target for anti-coagulant development in recent years. We designed a new mutant form of FXIa catalytic domain rhFXI370-607 （N73Q-N113Q-C123S）, and report here the facile preparation, protein crystallization, and crystal structure of this protein. We highlight a few unique structural features of FXIa after comparison with the trypsin family serine proteases at sequence and structural levels. This work provides a foundation to develop new small molecular FXIa inhibitors with increased potency and specificity.

In silico evidence of Remdesivir action in blood coagulation cascade modulation in COVID-19 treatment

BACKGROUND Coronavirus disease 2019(COVID-19)has demonstrated several clinical manifestations which include not only respiratory system issues but also liver,kidney,and other organ injuries.One of these abnormalities is coagulopathies,including thrombosis and disseminated intravascular coagulation.Because of this,the administration of low molecular weight heparin is required for patients that need to be hospitalized.In addition,Remdesivir is an antiviral that was used against Middle East Acute Respiratory Syndrome,Ebola,Acute Respiratory Syndrome,and other diseases,showing satisfactory results on recovery.Besides,there is evidence suggesting that this medication can provide a better prognosis for patients with COVID-19.AIM To investigate in silico the interaction between Remdesivir and clotting factors,pursuing a possibility of using it as medicine.METHODS In this in silico study,the 3D structures of angiotensin-converting enzyme 2(ACE2),Factor I(fibrinogen),Factor II(prothrombin),Factor III(thromboplastin),Factor V(proaccelerin),Factor VII(proconvertin),Factor VIII(antihemophilic factor A),Factor IX(antihemophilic factor B),Factor X(Stuart-Prower factor),and Factor XI(precursor of thromboplastin(these structures are technically called receptors)were selected from the Protein Data Bank.The structures of the antivirals Remdesivir and Osetalmivir(these structures are called ligands)were selected from the PubChem database,while the structure of Atazanavir was selected from the ZINC database.The software AutoDock Tools(ADT)was used to prepare the receptors for molecular docking.Ions,peptides,water molecules,and other ones were removed from each ligand,and then,hydrogen atoms were added to the structures.The grid box was delimited and calculated using the same software ADT.A physiological environment with pH 7.4 is needed to make the ligands interact with the receptors,and still the software Marvin sketch®(ChemAxon®)was used to forecast the protonation state.To perform molecular docking,ADT and Vina software was connected.Using PyMol®software and Discovery studio®software from BIOVIA,it was possible to analyze the amino acid residues from receptors that were involved in the interactions with the ligands.Ligand tortions,atoms that participated in the interactions,and the type,strength,and duration of the interactions were also analyzed using those software.RESULTS Molecular docking analysis showed that Remdesivir and ACE2 had an affinity energy of-8.8 kcal/moL,forming a complex with eight hydrogen bonds involving seven atoms of Remdesivir and five amino acid residues of ACE2.Remdesivir and prothrombin had an interaction with six hydrogen bonds involving atoms of the drug and five amino acid residues of the clotting factor.Similar to that,Remdesivir and thromboplastin presented interactions via seven hydrogen bonds involving five atoms of the drug and four residues of the clotting factor.While Remdesivir and Factor V established a complex with seven hydrogen bonds between six antiviral atoms and six amino acid residues from the factor,and Factor VII connected with the drug by four hydrogen bonds,which involved three atoms of the drug and three residues of amino acids of the factor.The complex between Remdesivir and Factor IX formed an interaction via 11 hydrophilic bonds with seven atoms of the drug and seven residues of the clotting factor,plus one electrostatic bond and three hydrophobic interactions.Factor X and Remdesivir had an affinity energy of-9.6 kcal/moL,and the complex presented 10 hydrogen bonds and 14 different hydrophobic interactions which involved nine atoms of the drug and 16 amino acid residues of the clotting factor.The interaction between Remdesivir and Factor XI formed five hydrogen bonds involving five amino acid residues of the clotting factor and five of the antiviral atoms.CONCLUSION Because of the in silico significant affinity,Remdesivir possibly could act in the severe acute respiratory syndrome coronavirus 2 infection blockade by interacting with ACE2 and concomitantly act in the modulation of the coagulation cascade preventing the hypercoagulable state.

Effects of low molecular weight heparin on the function of blood coagulation and serum levels of TNF-α, CK-MB, CRP of patients with acute exacerbations of chronic obstructive pulmonary diseases and respiratory failur

Objective:To study the effects of low molecular weight heparin on the function of blood coagulation and serum levels of tumor necrosis factor-α(TNF-α), creatine kinase isoenzyme (CK-MB), C-reactive protein (CRP) of patients with acute exacerbations of chronic obstructive pulmonary diseases and respiratory failure.Methods:A total of 80 patients with acute exacerbations of chronic obstructive pulmonary diseases and respiratory failure in our hospital from June 2014 to October 2016 were enrolled in this study. The subjects were divided into the control group (n=40) and the treatment group (n=40) randomly. The control group were treated with conventional treatment, the treatment group were treated with the conventional treatment combined with low molecular weight heparin. The two groups were treated for 7 d. The D-dimer (D-D), fibrinogen (FBG), pro thrombin time (PT), thrombin time (TT), TNF-α, CK-MB and CRP of the two groups before and after treatment were compared.Results:There were no significantly differences of the blood levels of D-D, FBG, PT and TT of the two groups before treatment. After treatment, the blood levels of D-D and FBG of the two groups were significantly lower than before treatment, and that of the treatment group were significantly lower than the control group, the PT and TT of the two groups were significantly higher than before treatment, and that of the treatment group were significantly higher than the control group. There were no significantly differences of the serum levels of the TNF-α, CK-MB and CRP of the two groups before treatment. After treatment, the serum levels of the TNF-α, CK-MB and CRP of the two groups were significantly lower than before treatment, and that of the treatment group were significantly lower than the control group.Conclusion:Low molecular weight heparin can significantly reduce the inflammatory factors of the patients with acute exacerbations of chronic obstructive pulmonary diseases and respiratory failure, can alleviath the patients conditions and reduce the myocardial damage.

中国血友病A患者因子Ⅷ抑制物形成特征及随访研究

目的随访研究中国血友病A患者因子Ⅷ(FⅧ)抑制物发生率和特征。方法 215例血友病A患者在24月(2007年6月至2009年6月)的连续随访中,监测FⅧ抑制物发生、变化及转归,并观察患者临床特征。结果 215例血友病A患者随访24月FⅧ抑制物累积发病率为11.6%(25/215);其中低滴度者占72%(18/25),高滴度者占28%(7/25);FⅧ抑制物阳性发生时的中位年龄为25岁(6～59岁)、累积中位暴露日为150日;15/25(60%)低滴度阳性者(中位滴度1.25BU/ml)在自然情况下于6～15月(中位10月)转为阴性,5/25(20%)高滴度抑制物者(中位滴度100BU/ml)则随访24月持续阳性,另外5/25(20%)FⅧ抑制物阳性无变化;25例FⅧ抑制物阳性者出血频率较其阴性时显著增加(P=0.025);18/25例继续应用FⅧ者,FⅧ产品用量(IU/kg·月)较前显著增加(P=0.015),但靶关节数目在24月随访期间并无增加(P=0.329)。结论我国血友病A患者FⅧ抑制物发病率和特征与欧美等国家存在差异。

B区缺失的人凝血因子Ⅷ基因在293T细胞表达

本研究目的是构建含有人凝血因子Ⅷ(FⅧ)基因的慢病毒载体,观察其在293T细胞中的表达情况。用限制性内切酶法获得B区缺失的人凝血因子Ⅷ基因(BDDhFⅧcDNA)片段,将其克隆至慢病毒载体pXZ208,构建了慢病毒表达载体pXZ208-BDDhFⅧ;用限制性内切酶法鉴定载体的连接方向,用磷酸钙共沉淀法将重组质粒pXZ208-BDDhFⅧ分别与包装质粒ΔNRF、包膜蛋白质粒VSV-G共转染293T包装细胞,包装后感染293T细胞,并以pXZ171作为对照。在感染后用逆转录-聚合酶链反应(RT-PCR)检测BDDhFⅧ基因的转录,一期法检测细胞培养上清FⅧ的活性,流式细胞仪(FCM)检测载体的感染效率,PCR检测BDDhFⅧ基因的整合。结果表明:成功构建了慢病毒表达载体pXZ208-BDDhFⅧ,其基因转导染效率达到了59.57%。RT-PCR法能够检测到BDDhFⅧ转录的mRNA。感染后24、48、72小时检测到细胞上清中FⅧ活性(FⅧ∶C)分别为12%、43%、87%。PCR法扩增出了534bp的特异性片段。结论:成功构建的慢病毒表达载体pXZ208-BDDhFⅧ,在体外可以有效感染293T细胞并表达有活性的FⅧ,提示基因治疗可应用于血友病A。

超大孔离子交换制备色谱分离纯化高活性凝血因子Ⅷ

建立了一条从人血浆中分离高活性凝血因子Ⅷ(FⅧ)的纯化工艺。基于FⅧ和介质孔径的尺度比及其对蛋白质活性影响的分析,设计了以超大孔离子交换制备色谱为核心步骤的新型分离纯化工艺。分别进行超大孔离子交换色谱与传统离子交换色谱的条件优化,并对优化工艺所得产品进行了活性检测(底物显色法)和纯度检测(高效凝胶过滤和凝胶电泳)。结果表明,超大孔介质结构不但可以有效地保护蛋白质大分子结构,而且能够大幅度地提高制备色谱的传质速率,从而得到具有高凝血活性的FⅧ产品。FⅧ在超大孔制备色谱过程中的回收率(85%)比传统离子交换制备色谱高4～5倍,产品比活高达154 IU/mg。此外,还研究了超大孔介质的再生程序,采用5个柱体积的1 mol/L NaOH低流速清洗色谱柱,保证了色谱工艺的稳定性。本纯化工艺步骤简单,重现性好,易于放大生产。

蛋白C、抗凝血酶及凝血因子Ⅷ活性变化与肺癌合并肺栓塞后治疗的关系

目的探讨蛋白C（PC）、抗凝血酶（AT）及凝血因子Ⅷ（FⅧ）活性变化与肺癌合并肺血栓栓塞[简称肺栓塞（PE）]后治疗的关系.方法选择肺癌合并PE患者（肺癌＋PE组）98例及肺癌患者（肺癌组）100例.记录两组性别、年龄并检测脂蛋白（a）[Lp（a）]、总胆固醇（TC）、甘油三酯（TG）、C反应蛋白（CRP）、凝血酶时间（TT）、血小板数量（PLT）、纤维蛋白原（Fbg）等指标.检测肺癌＋PE组治疗5～7d及肺癌组入院时的PC、AT、FⅧ、D-二聚体水平.应用Logistic回归分析肺癌合并PE后治疗5～7d凝血纤溶状态的影响因素,并采用受试者工作特征（ROC）曲线分析影响因素的诊断效能.结果肺癌＋PE组Lp（a）、TC、TG、TT均明显高于肺癌组（P〈0.05）.肺癌＋PE组PC、AT、FⅧ、D-二聚体水平明显高于肺癌组（P〈0.01）.Logistic逐步回归及ROC曲线分析显示,PC、AT、FⅧ是肺癌合并PE后治疗5～7d凝血纤溶状态的影响因素,ROC曲线下面积均〉0.90.结论肺癌合并PE中期治疗需关注PC、AT、FⅧ对凝血纤溶系统的影响,其活性水平可用来评估-定时期内的治疗效果和治疗方案.

凝血因子Ⅻ及Ⅷ在主动脉夹层围术期凝血功能中的作用研究

目的探讨凝血因子Ⅻ及凝血因子Ⅷ在主动脉夹层手术患者围术期的变化及对二次开胸的影响。方法选取2014年1月至2015年9月于首都医科大学附属北京安贞医院就诊的Stanford A型主动脉夹层患者88例,均接受中度低温停循环手术治疗。根据是否二次开胸将88例患者分为二次开胸组(10例)和未二次开胸组(78例),比较2组患者手术及术后重要指标,分析凝血功能障碍导致二次开胸的危险因素。选择麻醉诱导后(t1)、术中温度最低点(t2)、复温至36℃(t3)、术后4 h(t4)、术后24 h(t5)5个时点进行血液样本的抽取,应用酶联免疫吸附法进行凝血因子Ⅻ、活化的凝血因子Ⅻ、凝血因子Ⅶ、活化的凝血因子Ⅶ、凝血因子Ⅷ、活化的凝血因子Ⅷ、血红蛋白、血小板计数的检测。结果t2~t4时点凝血因子Ⅻ水平均低于t1,差异均有统计学意义(均P<0.05),t5时点与t1比较差异无统计学意义(P=0.065)。活化的凝血因子Ⅻ和活化的凝血因子Ⅷ水平由t1~t5全程呈逐渐升高趋势,与t1比较差异均有统计学意义(均P<0.05)。凝血因子Ⅷ水平各时点均低于t1,差异均有统计学意义(均P<0.05)。凝血因子Ⅶ水平于t2和t3时点均低于t1,t4和t5时点均高于t1,差异均有统计学意义(均P<0.05)。二次开胸组术中失血量、术后总引流量以及悬红细胞输注总量、冰冻血浆输注总量、纤维蛋白原输注总量均高于未二次开胸组[1 700(1 375,2 000)ml比1 250(1 000,1 600)ml;4 250(2 533,7 060)ml比2 170(1 230,3 555)ml;2 700(1 125,3 825)ml比675(600,1 424)ml;1 200(400,1 550)ml比400(50,800)ml;2.00(2.00,2.88)g比2.00(1.00,2.00)g],t2时点血小板计数水平低于未二次开胸组[(61±28)×109/L比(72±39)×109/L],差异有统计学意义(P<0.05)。在校正体质量、体外循环时间、手术时间、低温停循环时间、术前血小板水平、术前血红蛋白水平等因素的影响后,多元Logistic回归分析发现,t2时点凝血因子Ⅻ水平(比值比=1.342,95%置信区间:1.058~1.570,P=0.012)为主动脉夹层患者接受外科手术后凝血功能障碍导致二次开胸的独立危险因素。结论凝血因子Ⅻ作为内源性凝血途径的启动因子,在主动脉夹层患者围术期的凝血功能中发挥着巨大作用,其在术中最低温时的水平较低可能是术后由于凝血功能障碍导致二次开胸的独立危险因素;而凝血因子Ⅷ作为凝血共同途径的重要因子,本研究未发现其增加二次开胸的风险。

非病毒载体介导的人凝血因子Ⅷ基因在小鼠32D细胞系中的表达

为了观察非病毒载体 pRC/RSV介导的人凝血因子Ⅷ基因在小鼠 32D细胞系中的表达 ,将B结构域缺失(△ 76 0aa - 16 39aa)的人FⅧcDNA(hFⅧBDcDNA)亚克隆至质粒载体pRC/RSV ,构建重组质粒载体 pRC/RSV hFⅧBDcDNA。经SuperFectTransfectionReagent转染小鼠 32D细胞系 ,分别采用一期法、ELISA法和RT PCR检测细胞培养上清液中人FⅧ的促凝活性 (hFⅧ∶C)和抗原含量 (hFⅧ∶Ag)以及细胞中hFⅧBDcDNA的转录。结果表明 :小鼠 32D细胞系培养上清液中的人FⅧ∶Ag最高达到了 4 5 0 .0 8毫微克 /(10 6细胞·2 4小时 ) ,hFⅧ∶C最高达到了 2 .0 1单位 /(10 6细胞·2 4小时 ) ,RT PCR可检测到 32D细胞中hFⅧBDcDNA转录的mRNA。结论 :非病毒质粒载体 pRC/RSV介导的人凝血因子Ⅷ基因能够在小鼠 32D细胞系中表达人FⅧ蛋白 ,所表达的FⅧ与正常人血浆中的野生型FⅧ具有相似的凝血活性。

人凝血因子ⅧcDNA在小鼠体内的转染与表达

本研究观察逆转录病毒载体和聚酰胺 胺型 (PAMAM)树枝状聚合物介导的人凝血因子Ⅷ (FⅧ )基因在小鼠体内的转染和表达 ,并与体外转染方法作比较。应用含B区缺失 ( 76 0aa- 16 39aa)人FⅧcDNA(FⅧBDcDNA)的以逆转录病毒为框架的重组表达质粒载体 pLNC FⅧBD包装成为逆转录病毒LNC FⅧBD ,exvivo转染小鼠骨髓基质细胞 ,同时将 pLNC FⅧBD与PAMAM树枝状聚合物按照 1∶15混合以形成复合体PAMAM pLNC FⅧBD进行小鼠invivo转染。分别于注射后第 2 4 ,4 8小时 ,第 1,2 ,3,4周取血 ,分离血浆 ,采用一期法测定人FⅧ活性 (FⅧc) ,ELISA法测定人FⅧ抗原 (FⅧAg) ,并采用Bethesdainhibitorassay测定人FⅧ抗体 ;同时取脏器肝、脾、肺、肾提取RNA ,进行RT PCR ,观察各组织的转录 ,并用苏木素 伊红染色法观察各组织的形态学改变。结果表明 ,逆转录病毒转染人FⅧ基因的骨髓基质细胞输入体内后 ,可以在体内继续表达人FⅧ ,并且能有效地分泌至血液中。宿主小鼠体内可检测到的人FⅧ表达持续 3周以上 ,注射后第 2 4小时表达最高水平 ,人FⅧAg平均为 8.6ng/ml,此后人FⅧ抗体逐渐生成 ,人FⅧAg水平渐低 ,于注射后第 4周不再能测出人FⅧAg。注射复合体PAMAM pLNC FⅧBD在体内转染后 ,获得了短暂的人FⅧ生理水平的表达 ,在注射?

中和低剂量重组人凝血因子Ⅷ防治血友病A关节出血的疗效

目的 比较中、低剂量重组人凝血因子Ⅷ防治血友病A关节出血的临床疗效.方法将58 例血友病A患儿按预防剂量的大小分为2组：中剂量组（28例）和低剂量组（30例）.中剂量组采用重组人凝血因子Ⅷ15～25 ·kg-1静脉推注,3次周-1,连用4个月;低剂量组采用重组人凝血因子Ⅷ＜15 U·kg-1静脉推注,3次＆#183;周-1,连用4个月.观察2组防治前、防治4个月后关节出血次数的情况.结果 2组防治4个月后关节出血次数明显低于防治前（P＜0.05）,中剂量组防治4个月后关节出血次数明显低于低剂量组（P＜0.05）.结论 重组人凝血因子Ⅷ用于防治血友病A能明显改善关节出血症状,且中剂量防治优于低剂量.

215例血友病A患者因子Ⅷ抑制物形成的环境因素研究

目的研究中国血友病A患者因子Ⅷ(FⅧ)抑制物形成的环境因素。方法监测215例血友病A患者在2年(2007年6月至2009年6月)的连续随访中,FⅧ抑制物发生、变化及转归,并对FⅧ抑制物形成的环境因素进行回顾性分析。结果 215例血友病A患者随访2年FⅧ抑制物累积发生率为11.6%(25/215)。FⅧ抑制物形成的环境因素的多变量分析结果示:①输注原因中短期低剂量预防治疗比按需治疗形成FⅧ抑制物的风险低(OR=0.037,95%CI为0.002～0.616);②血友病越严重,累积暴露日越少,FⅧ抑制物形成风险越高;③发生严重出血事件是FⅧ抑制物形成的高危因素(OR=117.045,95%CI为19.333～708.617);④输注形式和发生重大感染事件与FⅧ抑制物形成无关。结论在中国目前治疗情况下,血友病患者FⅧ抑制物的形成可能与血友病严重程度、输注原因(预防治疗或按需治疗)、累积暴露日和是否发生严重出血事件有关。

尿激酶对动脉粥样硬化患者血清纤维蛋白原、凝血因子Ⅴ和凝血因子Ⅷ的影响

目的探讨尿激酶对动脉粥样硬化患者血清纤维蛋白原、凝血因子Ⅴ和凝血因子Ⅷ的影响,以评价尿激酶对动脉粥样硬化患者凝血功能的影响。方法选择2011年2月~2013年1月期间来在本院诊断为动脉粥样硬化的100例患者,并接受尿激酶静脉注射治疗。根据临床分期分成隐匿期(n=25)、缺血期(n=25)、坏死期(n=25)和纤维化期(n=25)。检测所有患者治疗前后血清纤维蛋白原、凝血因子Ⅴ和凝血因子Ⅷ浓度,并计算各指标的变化率。结果治疗后各组纤维蛋白原(Fg)、凝血因子Ⅴ(FⅤ)和凝血因子Ⅷ浓度均显著低于治疗前(P<0.05)。血清纤维蛋白原变化率隐匿组为(52.11±1.47)%,缺血组为(52.21±1.22)%,坏死组为(49.89±1.43)%,纤维化组为(50.73±1.71)%,各组间比较差异均无统计学意义。凝血因子Ⅴ变化率隐匿组为(62.83±2.25)%,缺血组为(62.63±1.92)%,坏死组为(60.89±2.11)%,纤维化组为(61.36±2.14)%,各组间比较差异均无统计学意义。凝血因子Ⅷ变化率隐匿组为(43.02±2.28)%,缺血组为(42.04±2.13)%,坏死组为(39.99±2.93)%,纤维化组为(40.93±2.94)%,各组间比较差异均无统计学意义。结论尿激酶可通过降低动血清纤维蛋白原、凝血因子Ⅴ和凝血因子Ⅷ浓度来降低动脉粥样硬化患者凝血功能,以达到抑制血栓形成的作用。

ABO血型、性别和年龄对血浆成分中Ⅷ因子和纤维蛋白原含量的影响

目的探讨ABO血型、性别、年龄对血浆成分中Ⅷ因子活性(FⅧ)和纤维蛋白原含量(FIB)的影响。方法采用离心法制备冷沉淀凝血因子和去冷沉淀血浆,检测献血者ABO血型、冷沉淀凝血因子与去冷沉淀血浆中Ⅷ因子活性和纤维蛋白原含量,并采用t检验,LSD法及多元线性逐步回归对各组数据进行分析。结果冷沉淀凝血因子中FⅧ水平以A型、B型组明显高于O型组(P <0.001),去冷沉淀血浆中FⅧ水平以A型、O型组明显低于B型组(P <0.01)。冷沉淀凝血因子中FI B水平以女性组明显高于男性组(P <0. 005),去冷沉淀血浆中FI B水平以女性组明显高于男性组(P <0. 05)。去冷沉淀血浆中FⅧ水平以>30岁人群明显高于≤30岁人群(P <0.05),去冷沉淀血浆中FIB水平以>30岁人群明显高于≤30岁人群(P <0.001)。结论血型是冷沉淀凝血因子和去冷沉淀血浆中FⅧ水平的影响因素,B型含量均是最高。ABO血型对冷沉淀凝血因子和去冷沉淀血浆中FIB水平无影响。性别是冷沉淀凝血因子中FⅧ和FIB水平的影响因素,也是去冷沉淀血浆中FIB水平的影响因素,且女性组高于男性组。年龄是去冷沉淀血浆中FⅧ和FIB水平的影响因素,适龄献血人群中>30岁组明显高于≤30岁组。

骨折端Ⅷ因子相关抗原与血流量的实验研究

目的 研究骨折愈合过程中骨折端Ⅷ因子相关抗原和血流量变化的规律及其相关性。方法 选用 35只大耳白兔制作左侧桡骨骨折动物模型 ,分别于伤后 8、2 4、72h ,1、3、5、8周利用单光子放射计算机断层显像术 (SinglePhotonEmissionComputerizedTomography ,SPECT)测定骨折端血流量变化 ,之后取骨折端标本提取蛋白样本定量检测Ⅷ因子相关抗原。结果 骨折端血流量在致伤后 8h开始上升 ,1周时达顶峰 ,高血流量状态一直维持到第 3周 ,第 5和第 8周基本恢复到正常水平 ;骨折端Ⅷ因子相关抗原在伤后 2 4h开始增高 ,骨折后 3天达到较高的水平 ,该状态一直维持到骨折后的第 3周 ,到第 5周时开始出现较明显的回落 ,第 8周时基本恢复到正常水平。结论 伤后 72h骨折端血流量增高与骨折端血管生成有关 ,早期的血流量增加可能与骨折后的创伤反应有关。